Low predictive value of PGL-I serology for the early diagnosis of leprosy in family contacts: results of a 10-year prospective field study in French Polynesia.

In 1983, a cohort study to follow up the family contacts of leprosy cases was implemented in French Polynesia to assess the usefulness and applicability of phenolic glycolipid-I (PGL-I) serology in a leprosy control program. A total of 1201 contacts (666 females, 535 males) have been included in the study. The IgM anti-PGL-I seroprevalence determined on the initial sera was 17%. It was significantly higher among females than males (20% vs 15%, p = 0.02). From 1983 to 1992, 4 out of 204 (2%) anti-PGL-I seropositive contacts developed the disease (1 indeterminate, 1 BT, 1 BL, 1 LL) compared with 10 out of 997 (1%) seronegative contacts (4 indeterminate, 3 BT, 1 BB, 2 TT). Of these 10 patients, only 3 (2 indeterminate, 1 BT) converted to seropositivity when leprosy was diagnosed. The risk of developing leprosy was not significantly higher among seropositive than among seronegative groups (2% vs 1%, p = 0.2). A PGL-I circulating antigen test performed on 216 selected sera at entry into the trial showed a higher antigen prevalence when the antibody level was higher. PGL-I antigen was detectable in 5 of 12 patients tested prior to diagnosis (1 LL, 1 BL, 3 indeterminate). The median time to externalize the disease was not significantly different among antibody-positive and -negative contacts (17 vs 25 months, p = 0.3). The relative risk of developing leprosy for contact individuals was 30.8 times that of noncontacts, and 15% of the total new cases detected between 1983 and 1992 emerged from the study population.(ABSTRACT TRUNCATED AT 250 WORDS)

Tuberculosis in leprosy patients detected between 1902 and 1991 in French Polynesia.

From 1902 onward, notification and follow up of leprosy patients has been systematic in French Polynesia. Since 1960, a tuberculosis control program and a register has also been implemented. From 1902 to 1959, 673 cases of leprosy were detected [346 multibacillary (MB), 138 paucibacillary (PB), and 179 unclassified due to the loss of medical files by the time of classification which was done during the 1980s]. Of these 673 cases, 89 (13.2%) died from tuberculosis, giving a mean annual death rate of tuberculosis in leprosy patients of 232 per 100,000. Mortality from tuberculosis in leprosy patients detected between 1901 and 1930 was 20.7%, and decreased to 8.04% in patients detected from 1931 to 1959. In total, it was estimated that 26.4% of the leprosy cases had developed tuberculosis. From 1960 to 1991, 350 new cases of leprosy were detected (141 MB, 209 PB). Of them, 12 (3.4%) developed tuberculosis (7 before detection of leprosy, 5 after detection of leprosy). The dramatic decrease of the proportion of leprosy patients who developed tuberculosis between the periods 1902-1959 (26.4%) and 1960-1991 (3.4%) might be related to the important decline of the tuberculosis situation since 1960. From 1902 to 1959, mortality from tuberculosis occurred significantly more frequently in MB patients (13%) than in PB patients [4%, relative risk (RR) = 3.21, p = 0.003]. From 1960 to 1991, the incidence of tuberculosis seemed more frequent in MB patients (RR = 2.96, p = 0.07) whatever the sequence of detection of the two diseases. Our study suggests that lepromatous patients could share factors of susceptibility to mycobacterial diseases with patients developing tuberculosis.

Chemoprophylaxis of leprosy with a single dose of 25 mg per kg rifampin in the southern Marquesas; results after four years.

In January-February 1988, a program of chemoprophylaxis for leprosy, using a single 25 mg/kg dose of rifampin, was conducted among 2786 (98.7%) inhabitants of the Southern Marquesas and 3144 South Marquesan "emigrants" and their families. Among the treated population, during the 4 years which followed the implementation of the program, two leprosy patients were detected, one of whom can be considered as a failure of chemoprophylaxis because she was not known by the leprosy control unit. During the same period (1988-1991), a decrease in detection rates for leprosy in the entire French Polynesian population has been observed, an event which makes the interpretation of these findings very difficult. Nevertheless, according to presently available data, the effectiveness of chemoprophylaxis with a single dose of 25 mg/kg rifampin is estimated to be about 40% to 50%. When considering not only the results of the present study but also the financial and logistic constraints raised by such a program, one is led to the conclusion that chemoprophylaxis, even with a single dose of rifampin, is not likely to become an effective component of leprosy control programs.

Leprosy in French Polynesia. Epidemiological trends between 1946 and 1987.

The analysis of computerized data (OMSLEP system) on patients from French Polynesia followed since 1940 has shown a decrease in the mean annual detection rates for leprosy, all forms combined, from 24.73 per 100,000 inhabitants in 1946 to 8.1 per 100,000 in 1987 (y = -0.49 x + 45.83; p < 0.05). In fact, the decrease was significant (y = -1.18 x + 83.54; p < 0.05) during the first half of the study period (1946-66), but not during the second half (1967-87). Similarly, a significant decrease in all of the specific mean annual detection rates (according to the form of leprosy and to the sex and age of patients), in the proportion of multibacillary patients among the total of newly detected cases, and in the proportion of all patients with disabilities at the onset of leprosy was observed only during the first half of the study period (1946-66). Nevertheless, when comparing age-specific cumulative detection rates, calculated by 10-year age groups over the period 1946-66, to those of the period 1967-87, an ageing of the leprosy population was noted. Finally, the decrease of mean annual detection rates was greater in the smaller populations of remote islands than in the population of Tahiti, the main island, where 70% of the total population were living during the study period. This decline was shown to correspond to an effective improvement of the leprosy situation which could be attributed, among other factors (such as economic development and systematic BCG vaccination), to the implementation of a control programme for leprosy in 1950. The introduction in 1982 of multidrug therapy for all patients suffering active leprosy has raised the hope of a subsequent decline of leprosy in French Polynesia in the near future.

Longitudinal study on relapses of leprosy in Polynesian multibacillary patients on dapsone monotherapy between 1946 and 1970.

Between 1946 and 1970, 295 new leprosy patients were detected in French Polynesia, of whom 145 were multibacillary. Of these 145, put on dapsone monotherapy, 131 reached bacteriological negativity in a period of time ranging from 2 to 12 years (average 4.72 years) and were followed-up for a period of time ranging from 19 to 43 years (median follow-up period after bacteriological negativity; 18 years). Among the 131 patients, 36 relapses were detected, the first one 4 years after bacteriological negativity and the last one 26 years after. The crude relapse rate was 27.5%, the risk of relapse was 1.39 per 100 patient years and the cumulative relapse probability, calculated using the lifetable method, reached 0.38 +/- 11 by year 31 of the study. From these findings one may assume that, at least in French Polynesia, one-third to one-half of multibacillary patients put on dapsone monotherapy would relapse if still present 36 years after bacteriological negativity. Such results re-emphasize the need for leprosy patients to be treated with multidrug therapy as recommended by WHO.

Assessment of anti-phenolic glycolipid-I IgM levels using an ELISA for detection of M. leprae infection in populations of the South Pacific Islands.

Anti-phenolic glycolipid-I (PGL-I) IgM levels were determined in 96% of the general population of the Southern Marquesas and Maupiti, remote islands of French Polynesia, where the average annual detection rates of leprosy during the past 30 years have been 57.1 and 4.4 per 100,000, respectively. The seropositivity in these two areas was 4.3% and 4.2%, respectively. No significant difference (p greater than 0.05) was found between either these two figures or between the percentages of persons with high (greater than or equal to 0.500 OD) anti-PGL-I IgM levels (9.2% and 5.3%). In the two islands, the age distributions of anti-PGL-I IgM were very similar; the percentage of positive responders was higher in females than in males and higher in adolescents than in adults. These results suggest that the usefulness of the determination of anti-PGL-I IgM levels by ELISA, using the synthetic trisaccharide as antigen, for detecting Mycobacterium leprae infection in leprosy control programs is extremely doubtful.

[The detection of IgM antibodies to phenolglycolipid I for serodiagnosis of Hansen's disease and monitoring the contact population in Polynesia. Five year evaluation]. / La détection des IgM anti-PGLI pour le sérodiagnostic des malades hanséniens et la surveillance des sujets contacts en Polynésie. Bilan sur 5 ans.

This study was conducted to assess the usefulness of IgM anti-PGLI antibody test, for the diagnosis of leprosy and of the subclinical infection among contact population. Even if the specificity (97.7%), sensitivity (98% for the multibacillary, but 36% for the paucibacillary) and efficiency (97.7%) of the test for the diagnosis of patients are good, its positive predictive value which is the proportion of true patients among the seropositive subjects detected in the population was very low (1.17% in Polynesia), because of the very low prevalence of leprosy. For the diagnosis of the subclinical infection, our experience based on the follow up of a population of 1,123 contacts, showed that such a control program would have low feasibility and low cost-effectiveness. After 5 years, the proportion of individuals developing the disease was not different among the seropositive than among the seronegative subjects. Finally, only 17.5% of the new cases of leprosy detected, were issued from the contact population followed. In conclusion and in a practical point of view, although this test may contribute to the diagnosis of patients, it is not likely useful neither for the diagnosis nor for the prognosis of leprosy in a population.

PGL-I antigen and antibody detection in leprosy patients: evolution under chemotherapy.

Multibacillary (MB) and paucibacillary (PB) leprosy patients were tested for circulating phenolic glycolipid-I (PGL-I) antigen and antibodies before treatment. In the 27 MB patients tested, 27 (100%) were antigen positive with levels ranging from 50 to 5000 ng/ml, and 26 (96%) were antibody positive with titers ranging from 1000 to 64,000. Although the antigen and antibody levels were much higher in MB than in PB patients, we could not demonstrate a correlation between the number of acid-fast bacilli/mg of skin biopsy and these two parameters in 14 MB patients. After starting daily multidrug therapy, 10 MB patients were monitored monthly. As much as 88.75% +/- 10.8% of the PGL-I antigen was cleared from the bloodstream after 1 month while the anti-PGL-I antibody remained stable. This rapid decrease in the PGL-I antigen level strongly suggests the usefulness of this test for monitoring MB patients under chemotherapy.

Implementation of chemoprophylaxis of leprosy in the Southern Marquesas with a single dose of 25 mg per kg rifampin.

Between 1967 and 1987 in the Southern Marquesas, a remote archipelago in French Polynesia, the detection rate of leprosy was 48.9 per 100,000 when it was 8.6 per 100,000 for French Polynesia as a whole. In 1988, a program of chemoprophylaxis of leprosy with a single dose of 25 mg/kg rifampin was implemented, and 2751 persons (98.7% of the population) were treated in the Southern Marquesas. In addition, 678 South Marquesans and 2466 members of their families living in the Northern Marquesas and in the Society Archipelago, received the same chemoprophylaxis. Among 2676 persons studied in the Southern Marquesas (97.4% of the treated population), 130 had elevated IgM anti-phenolic glycolipid-I antibodies by ELISA without any evidence of leprosy. The onset of a skin lesion of borderline leprosy in a boy 3 months after chemoprophylaxis raises the question of the nature of such a skin lesion and, indirectly, of the effectiveness of the chemoprophylaxis.

Finger-prick blood collection and computer-assisted enzyme-linked immunosorbent assay for large-scale serological studies on leprosy.

An immunoglobulin M anti-phenolic glycolipid 1 assay was standardized and optimized using specimens of dried blood collected on commercial precut filter paper discs, followed by a computer-assisted enzyme-linked immunosorbent assay (ELISA). The correlation between venepuncture and finger-prick methods, the calibration of the quantity of absorbed blood, and the reproducibility of the ELISA test were excellent. A slight decline of activity was observed when the samples were stored for 3 months at +4 degrees C. Skimmed milk can be used as diluent instead of bovine serum albumin, contributing to lessening the cost of the test. Using the method described, as many as 300 samples can be collected in the field and 480 ELISAs per day can be run in the central laboratory by one trained person.

Comparison of synthetic antigens for detecting antibodies to phenolic glycolipid I in patients with leprosy and their household contacts.

Three synthetic antigens related to the natural antigen phenolic glycolipid I (PGL-I) were compared for their efficacy in detecting leprosy when used as antigens in an enzyme-linked immunosorbent assay (ELISA) for IgM antibody to PGL-I. Absorbance values for ELISAs using the three antigens correlated well (.79 less than r less than .99) and had a high rate of agreement (89.5% less than a less than 98.4%). Of three subjects (household contacts of patients with leprosy) who later developed the disease, one with lepromatous and one with indeterminate leprosy were seropositive by ELISAs using the three antigens before the clinical onset of disease; one who developed borderline tuberculoid leprosy was seronegative. The predictive value of a positive result for the test was very low (less than 2.4%) and the predictive value for a negative result was high (greater than 99.9%) because of the low prevalence of leprosy in French Polynesia (1.78 per 1000). The high sensitivity, specificity, and efficiency of the tests using the three antigens confirmed their great value for serodiagnosis of leprosy, especially the multibacillary form; the ELISA using NTP seems to be more specific and sensitive for detecting the paucibacillary form.

[Leprosy in the French Polynesian archipelagoes from 1967 to 1987]. / La lépre dans les archipels de Polynésie française de 1967 à 1987.

Between 1967 and 1987, 255 new cases of leprosy were detected in French Polynesia (FP) that means on average a 8.6% detection rate. Average detection rate calculated in 7 three-year periods did not vary significantly during the 21 years studied period of time. In two remote archipelagoes of FP average detection rate of leprosy is specially high: Gambier archipelago and Southern Marquesas archipelago with respectively a 54.7 and a 48.9% detection rate. To control leprosy, the network of treatment and active case-finding should be strengthened in archipelagoes and chemoprophylaxis programmes could be planned in places where the problem is especially important.

Seroepidemiological study on 724 household contacts of leprosy patients in French Polynesia using disaccharide-octyl-BSA as antigen.

A seroepidemiological surveillance of a contact population was started in 1984 in French Polynesia. The ELISA test was used to measure IgM anti-ND-O-BSA in the sera. Specific antibody levels were higher in healthy Polynesians than in normal individuals living in a nonendemic country. The positive threshold of the reaction was fixed according to this background activity in healthy Polynesians. Under these conditions, 100% of the multibacillary patients were detected as seropositive as compared to 5% of the paucibacillary group. In the population of 724 household contacts tested and observed for 2 years: 93 (12.8%) were seropositive, with 8 (1.1%) showing activity equivalent to multibacillary patients (1 of these 8 individuals developed a lepromatous form of leprosy); 631 (87%) were seronegative and 3 developed a paucibacillary form of the disease (2 BT, 1 I) without any antibody increase. Among those four contacts who developed leprosy, three were related to a multibacillary index case. These data suggest that this test may be useful for the prediction of multibacillary leprosy. A long-term surveillance of this high-risk population will be able to evaluate the diagnostic and prognostic value of the serological assay.